Transmission of prion
brain diseases such as bovine spongiform enecephalopathy (BSE) – also
known as mad cow disease – and human variant Creutzfeldt-Jakob disease
(vCJD) is generally attributed to the consumption of the brain or organ
meat of infected animals but new research demonstrates lambs exposed to
milk from prion-infected sheep with inflamed mammary glands can develop
prion disease as well. The research, which is published in the January
2011 issue of the Journal of Virology, has major implications for human and livestock health.

“Prions cause
devastating, ultimately fatal infections in humans,” says corresponding
author Christina Sigurdson of the University of California, San Diego
School of Medicine. “This study is the first demonstration of prions
from an inflamed organ being secreted, and causing clinical symptoms in a
natural host for prion disease.”

Recent research had
suggested that human-to-human transmission of prions has occurred via
blood transfusions, “underscoring the importance of understanding
possible transmission routes,” the researchers write. The misfolded
prions that cause vCJD in humans, and BSE in cattle -- which can be
transmitted to humans -- commonly accumulate in lymphoid tissues before
invading the central nervous system, where they wreak their deadly
effects. Inflammation can cause lymphoid follicles to form in other
organs, such as liver and kidney, which leads prions to invade organs
that normally do not harbor infection. In recent research, this team,
led by Ciriaco Ligios of the Istituto Zooprofilattico Sperimentale in
Sardinia, Italy and Adriano Agguzi at the University of Zurich,
Switzerland, reported sheep with misfolded prions in inflamed mammary
glands, also known as mastitis, raising concerns that prions could be
secreted into milk.

In the new research, the
team infected sheep with a common retrovirus that causes mastitis, and
misfolded prions. They bred the sheep, in order to stimulate the females
to produce milk, which they then collected and fed to lambs that had
never been exposed to prions. The lambs developed prion disease after
only two years, a speed which surprised the researchers, and “suggested
that there was a high level of prion infectivity in milk,” says
Sigurdson.

The research raises several disturbing possibilities.

A common virus in a
sheep with prion disease can lead to prion contamination of the milk
pool and may lead to prion infection of other animals.

The same virus in a
prion-infected sheep could efficiently propagate prion infection within a
flock, through transmission of prions to the lambs, via milk. This
might be particularly likely on factory farms, where mastitis may be
common, and could occur in goats as well as sheep.

However, “This work
cannot be directly extrapolated to cattle,” says Sigurdson. She says
that BSE prions do not accumulate to detectible levels in lymphoid
organs, and thus would not be expected to accumulate with inflammation.
“Nonetheless,” she says, “it would be worth testing milk from cattle
with mastitis for prions as there may be other cellular sources for
prions entry into milk.”